Hereditary Retinoblastoma

Retinoblastoma is an eye cancer. It usually develops in children before age 5. This cancer develops in the retina. The retina helps a person see color and light. Retinoblastoma may affect 1 or both eyes.

There are 2 types of retinoblastoma:

• Hereditary (can be passed down in families). The hereditary form carries specific health risks that are not found with the sporadic form. Children with hereditary retinoblastoma are at an increased risk to:
  • Develop other tumors (such as more retinoblastoma tumors, pineal gland tumors, skin tumors, bone tumors, and muscle tumors)
  • Develop second cancers after exposure to radiation
  • Pass down the condition to some of their children
• Sporadic (not passed down in families). Children with sporadic retinoblastoma are not at an increased risk of passing the disease down to their children. Their risk for developing second cancers is much less than the risk for children with hereditary retinoblastoma.

It is important to know whether a person has hereditary retinoblastoma or the sporadic form of retinoblastoma. About 40% (4 in 10) of children with retinoblastoma have both eyes affected. These children always have the hereditary form.

About 60% (6 in 10) of children with retinoblastoma have only 1 eye affected. Most of these children have the sporadic form of retinoblastoma. About 15% (15 in 100) of children with only 1 eye affected have hereditary retinoblastoma.

Cancer risk with hereditary retinoblastoma

Hereditary retinoblastoma might start in just 1 eye. The chances of it developing in the other eye are high because cells in the other retina contain an RB1 gene.

Most children with hereditary retinoblastoma develop tumors affecting 1 or both eyes. The risk of developing retinoblastoma tumors is greatest during the first 5 years of life.

A small number of children with hereditary retinoblastoma develop cancers outside the eyes. This includes the pineal gland of the brain. Later in life, tumors might form in other parts of the body (bones, muscle, and skin).

Most children with retinoblastoma can be cured of the disease, especially if the disease is confined to the eyes. If left untreated, it can spread to other parts of the body. When it spreads, it becomes much harder to treat.

Hereditary retinoblastoma symptoms

Retinoblastoma is rare. Parents may notice 1 or more of the following symptoms:

• A white color to the pupil (the central portion of the eye that is usually black), especially with flash photos
• A misaligned or “lazy eye” that may turn outward or inward when the child looks straight ahead
• Vision problems
• Red or irritated eyes

The disease may be found during routine eye exams of babies and toddlers. When the disease is found, the child should be urgently referred to an eye specialist (an ophthalmologist).

Causes of hereditary retinoblastoma

Hereditary retinoblastoma is caused by changes in a gene known as RB1. Genes carry important information that tells our body’s cells how to function.

The RB1 gene controls how cells grow and divide. One of its main jobs is to prevent tumors from forming, particularly retinoblastoma.

How hereditary retinoblastoma is inherited

Cells from people with hereditary retinoblastoma carry 1 working copy of RB1 and 1 copy that is different. This difference (a mutation) causes the gene to not work right. When the remaining working copy of RB1 becomes damaged within a cell of the developing retina, it may lead to a retinoblastoma tumor.

In about 10–20% of hereditary retinoblastoma cases, this mutation is passed down from a parent who also has hereditary retinoblastoma. In the other cases, the affected child has a new mutation that was not present in either parent. This child is the first in the family to have hereditary retinoblastoma. But they can now pass on the disease to 50% (1 in 2) of their future children.
 

Hereditary retinoblastoma diagnosis

In about 80–90% of hereditary retinoblastoma cases, the child is the first person in the family to have the condition. In these cases, the RB1 mutation happened in either:

• An ovum (egg) or sperm cell that formed the child
• 1 of the child’s cells before they were born

Less often, a child will inherit hereditary retinoblastoma. This happens because the mother or father also carries the RB1 mutation and passes it on to the child.

Testing when eye tumor tissue is available

Retinoblastoma genetic testing is best performed by starting with a sample of the eye tumor. This can only be done if the entire eye is removed as part of disease treatment. A biopsy of the tumor is not performed. The disease can spread outside the eye when tumor cells are removed.

The lab will run a special type of genetic testing on a piece of the tumor. They will look for changes in the RB1 gene that might cause hereditary retinoblastoma.

Sometimes 2 RB1 mutations that led to the formation of the retinoblastoma tumor are found. When this happens, a separate blood sample is taken to see if 1 of these mutations is there.

Finding an RB1 mutation in the blood confirms a hereditary retinoblastoma diagnosis. The absence of an RB1 mutation in the blood usually means that the child has sporadic retinoblastoma.

Testing when eye tumor tissue is not available

RB1 genetic testing can be done on a blood sample from a child with retinoblastoma. This test can be done even when no eye tumor is available. But it is sometimes harder to interpret the test results for children with only 1 affected eye.

If an RB1 mutation is found, the child has hereditary retinoblastoma.

Hereditary retinoblastoma may still be there even if no RB1 mutation is found. For example, it is possible that a mutation is present, but it was not found because of limitations with the testing process. For this reason, all patients with retinoblastoma should have genetic counseling with an experienced health care provider.

RB1 genetic test results can provide important details for other family members. When an RB1 mutation is found, other family members can be tested to see if they carry the same mutation.

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known RB1 mutation. Testing may take place either before pregnancy occurs or during pregnancy.

You should work with a genetic counselor to review the pros and cons and availability of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known RB1 mutation before a provider places the embryo into the uterus.

Testing during pregnancy can help providers see if a pregnancy has a known RB1 mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

• Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
• Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for the RB1 mutation. Both tests carry minor risks. You should discuss the risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

If you decide not to undergo prenatal genetic testing, you should talk with your care team to plan for eye exams and possible genetic testing within weeks after your baby is born.

Sometimes, children or adults with hereditary retinoblastoma feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass the RB1 gene mutation to 1 or more of their children. People with an RB1 gene mutation may also have trouble getting disability or life insurance.

Read more about genetic discrimination. 

Monitoring and follow-up care for hereditary retinoblastoma

Children with hereditary retinoblastoma should be watched closely for eye tumors to develop. The goal is to detect cancer at the earliest and most treatable stage. Doing so helps minimize the therapy that is required. It also helps preserve vision.

A specialized eye doctor (an ophthalmologist) will conduct an eye exam as early as possible, even starting at birth, if there is a family history of retinoblastoma. Exams should then continue every 1–2 months during the first 2 years of life. The exams become less frequent as the child gets older. After age 5, regular yearly exams should occur for the rest of the child’s life. The doctor will decide how often the exams should take place.

There is a small risk of tumors forming in the pineal gland. The child should have a magnetic resonance imaging (MRI) scan of the brain twice a year through age 4.

As children with hereditary retinoblastoma grow up, they should continue to have regular physical checkups and screenings. They should also maintain a primary health care provider. That way, any cancer can be found early and at the most treatable stage.

Living with hereditary retinoblastoma

Problems to watch for

People with hereditary retinoblastoma should watch closely for symptoms that could signal cancer, such as:

• Weight loss that cannot be explained
• Loss of appetite
• Aches, pains, lumps, or swellings that cannot be explained
• Headaches or changes in vision or nerve function that do not go away.
• New moles or changes in moles that are already present

Parents of children, or young adults with hereditary retinoblastoma should seek medical help if these symptoms appear.

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

• Eat a healthy diet with lots of fruits and vegetables.
• Get regular exercise.
• Avoid smoking or using tobacco products.
• Avoid secondhand smoke.
• Avoid excess sun exposure and always wear sunscreen, a hat, and protective clothing when out in the sun.
• Pay attention to unusual symptoms that could be signs of a tumor.
• Avoid radiation exposure when possible.

Hereditary retinoblastoma care at St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers excellent clinical care. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions. Learn more about the Division of Cancer Predisposition at St. Jude.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

• A complete health history
• A record of cancer that happened over the past 3 generations (family tree) to see how diseases were passed down
• Physical exams to check for features of genetic conditions
• Confidential genetic counseling and testing
• Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
• Recommended cancer treatments and ways to reduce cancer risk
• Genetic testing for immediate (1st degree) relatives

Hereditary retinoblastoma increases your child’s risk for cancer.

Related clinical trials  

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancer associated with hereditary retinoblastoma .

Learn more about clinical research at St. Jude